Abstract 4373470: COX-1 RELATED THROMBOXANE OVERPRODUCTION IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION

Abstract

Introduction and hypothesis: Aging is associated with an increased incidence of cardiovascular events. Recent evidence suggest that platelets from older subjects differ in function and structure, are more susceptible to activation and less sensitive to inhibition. Atrial fibrillation is an interesting model to explore the topic as most patients were older than 65 years and few of them have a concomitant coronary artery disease needing aspirin therapy. Aim: to evaluate the association between age and serum TxB2 in a cohort of patients with atrial fibrillation receiving or not receiving aspirin therapy, and the behavior of platelet COX-1 and TxB2 in response to aspirin administration in a subgroup of them. Methods: Patients with non-valvular atrial fibrillation were prospectively included from 2013 to 2023. Serum and platelet TxB2, and platelet COX-1 were measured. Primary analysis included 134 patients with atrial fibrillation not receiving aspirin while secondary analysis 26 patients with atrial fibrillation receiving aspirin. In vitro experiments were performed in a subgroup of these latter (N=20). Baseline characteristics are reported as descriptive statistics. Spearman correlation and multiple linear regression were used to test the correlation between age and serum TxB2 values. Results: For primary analysis, 134 patients were included with a median age of 74 years. Arterial hypertension was present in 89.6% and diabetes mellitus in 38.7% of patients. A history of coronary artery disease in 15.1%. Median CHA2DS2-VA score was 3. A positive correlation has been found between age and serum TxB2 (R=0.45) with an increase in TxB2 of 11.6 ng/ml per each one-year of age increase. In secondary analysis, a positive correlation has been found between age and serum TxB2 (R=0.50) with an increase in TxB2 of 2.1 ng/ml per each one-year of age increase. In vitro study showed that Platelet TxB2 of older patients was not significantly reduced by aspirin; half maximal inhibitory concentration for platelets’ TxB2 production and COX-1 expression was higher in older patients, and a negative correlation between COX-1 expression and platelets’ TxB2 inhibition by ASA (R=-0.640) was found. Conclusion: TxB2 values significantly increased with aging in AF patients. This age-related increases in TxB2 production persisted during aspirin therapy and related to overexpression of COX-1 suggesting the need for different antiplatelet treatment in older AF patients.